The present invention generally relates to apheresis systems for separating one or more components from a cellular suspension such as blood. More specifically, the present invention relates to an improved apheresis system that limits the free flow of anticoagulant in the event of improper assembly or mechanical failure of the apheresis system.
The separation of blood into one or more component parts, such as platelets, red cells or plasma, has been well known for many years. Within the past twenty years, automated apheresis systems, which automatically process the blood of a donor or patient, separate out the desired blood component and return the remainder to the donor/patient, have become commonplace in developed countries.
Typically such automated apheresis systems employ a fluid circuit assembly, for example, a pre-assembled disposable plastic tubing and container set, which is mounted on a reusable hardware device. The reusable hardware device includes pumps, monitors, drive systems and the like for carrying out, in combination with the disposable fluid circuit assembly or system, a blood apheresis procedure.
There are several different automated apheresis systems commercially available. Baxter Healthcare Corporation, a pioneer in the field of automated blood apheresis, manufactures and sells the CS-3000 and Amicus centrifugal apheresis systems and the xe2x80x9cAutopheresis C,xe2x80x9d which is a non-centrifugal system, based on a different principle of blood separation. The Baxter CS-3000, Amicus and Autopheresis C apheresis systems are described, for example, in U.S. Pat. Nos. 4,526,515; 5,427,509; and 5,194,145, respectively, which are incorporated by reference. Centrifugal apheresis systems are also available from Cobe Laboratories Inc., which markets the Spectra apheresis system, and Haemonetics Corporation.
One of the characteristics of human blood is that it begins to clot immediately upon leaving the human vascular system. Accordingly, in automated apheresis systems, anticoagulant is used to prevent the donor/patient""s blood from clotting as it is processed through the fluid circuit of the apheresis system. One of the most common anticoagulants is ACD, (anticoagulant citrate dextrose), which is commercially available in various formulations. In automated apheresis systems, ACD is typically metered into the whole blood immediately after the blood is withdrawn from the donor/patient.
The amount of anticoagulant and the rate at which it is added to the donor/patient""s blood represents a balance of competing considerations. On the one hand, it is desirable to add sufficient anticoagulant so that the blood and blood components do not clot or clump as they are processed through the fluid circuit of the apheresis system. On the other hand, the flow rate of anticoagulant can not be too great or it will cause adverse reaction in the donor/patient.
A portion of the anticoagulant that is mixed with the whole blood is also returned to the donor/patient together with the blood components being returned. Specifically, the anticoagulant that is not removed with the blood components being collected is returned to the donor/patient with the remaining blood components. Although ACD anticoagulant is metabolized by the human body, if anticoagulant is returned to the donor/patient too fast it can, in fact, cause adverse reactions. Depending on the amount rate of anticoagulant returned, these reactions can range from mild physical symptoms, such as tingling of the lips or extremities, to potential actual harm to the donor/patient.
Accordingly, automated apheresis systems typically use pumps to control and meter the flow of anticoagulant added to the whole blood. The pumps used are commonly peristaltic pumps. peristaltic pumps use a series of spaced apart rollers that progressively pinch or squeeze the tubing to force fluid flow therethrough. When the tubing is properly installed in cooperation with the pump, peristaltic pumps tend to be very reliable and relatively accurate. Moreover, in the event of system shutdown or the like, at least one roller occludes the tubing to prevent undesired flow past the pump.
Although the manufacturers of automated apheresis systems have taken a variety of precautions by way of safety sensors and detectors to safeguard the donor/patient from operator inadvertence or error, continued diligence in identifying potential failure modes of apheresis systems has identified one scenario in which operator inattention or misassembly may result in larger than desired anticoagulant flow rates into the whole blood withdrawn from the donor/patient, with the potential result that more anticoagulant is returned to the donor/patient than is desirable.
More particularly, this scenario may occur if operator inattention or misassembly results in improper or incomplete installation of the anticoagulant tubing with the anticoagulant pump. In the typical apheresis system, the anticoagulant or ACD container is hung from a rack located over the apheresis device and above the donor/patient. This creates a liquid head of anticoagulant which, if not properly controlled by a pump, may cause an unrestricted or free flow of anticoagulant into the whole blood being withdrawn from the donor or patient. In other words, if the anticoagulant pump tubing segment is not properly engaged with the rollers of the pump, an open flow path may result, allowing an uncontrolled and free flow of excessive amounts of anticoagulant into the whole blood flow path. The result is an excess of anticoagulant being returned to the donor/patient, causing possible adverse reactions.
The present invention is directed to an apheresis system which, in the event of incomplete or improper installation of the anticoagulant tubing, whether by operator or mechanical failure, limits the free flow of anticoagulant into the whole blood flow path while preferably not completely stopping the flow of anticoagulant. As set forth in more detail below, the invention may be embodied in the disposable fluid circuit itself or in the combination of the disposable fluid circuit and apheresis device.
The present invention may be embodied, in accordance with one aspect, in a disposable apheresis fluid circuit or system. Such a system may include a separation chamber; a suspension flow path which communicates at one end with the separation chamber and includes a connector at the other end for connecting to a source of cellular suspension, such as blood from a donor/patient or concentrated blood component after initial apheresis processing; an anticoagulant flow path which communicates at one end with the suspension flow path, and includes a connector at the other end for connecting to an anticoagulant source; and a return flow path which communicates at one end with the separation chamber and communicates at the other end with a connector for connection directly to the suspension source or to the suspension flow path for returning one or more suspension components to the source.
In accordance with the present invention, the anticoagulant flow path includes a flow restriction, such as an internal flow restriction, which limits the free flow of anticoagulant into the suspension flow path. For example, it is preferred that the flow restriction limit the free flow of anticoagulant into the suspension flow path to less than about 14-15 milliliters per minute (ml/min) for donor/patient apheresis procedures.
More preferably, the flow restriction limits the free flow of anticoagulant to less than about 12.5 ml/min in a typical donor/patient apheresis procedure, with less than 8 ml/min but more than about 2-3 ml/min being more preferred. In general, an anticoagulant free flow rate of about 5 ml/min is most preferred with converging ranges of between 3-7 ml/min and 4-6 ml/min in order of preference.
In the apheresis field, it is also common to refer to the ratio of the whole blood flow rate to anticoagulant flow rate. This is sometimes referred to as the anticoagulant or AC ratio. In accordance with the present invention it is generally desirable that the flow restriction limit the free flow of anticoagulant to provide an AC ratio of not less than about 7/1 and not more than 13/1 in a free flow situation, i.e., the ratio of the suspension or blood flow rate to anticoagulant free flow rate.
Although the flow restriction may take different forms within the scope of the present invention, in one preferred embodiment an internal flow restriction is provided in the anticoagulant flow path in the form of a tubing segment which is of sufficiently small cross-sectional area and sufficient length to restrict the free flow of anticoagulant therethrough. The anticoagulant flow path may include a tubing segment, for example, which has a lumen from about 0.025 inches to about 0.05 inches in diameter. The required length of the tubing segment will vary inversely with the diameter to provide a given resistance to fluid flowxe2x80x94i.e., a larger diameter tubing will require greater length to provide the same resistance as a smaller diameter tubing.
Although the flow restriction may theoretically be provided at any location in the anticoagulant flow path, it is preferred that the flow restriction in the anticoagulant flow path be downstream of the anticoagulant pump so that pumping ACD at high flow rates does not lead to reduced pressure upstream of the pump of such magnitude that the upstream tubing might collapse and block anticoagulant flow. Also, with the flow restriction between the anticoagulant pump tubing segment and the suspension flow path, the flow restriction retards or restricts the free flow of anticoagulant in free flow conditions while simultaneously allowing the anticoagulant pump to generate enough pressure to pump anticoagulant through the flow restriction at flow rates that are normally used in the regular operation of the apheresis system. The flow restriction should, however, permit such pumped flow of anticoagulant without causing excessive pressure in the anticoagulant flow line. It is generally desired that pumped flow of up to about 14 ml/min of ACD anticoagulant be permitted without creating excessive pressure. Preferably, pumped flow of up to about 14 ml/min should not create pressure substantially greater than about 12 psig in the anticoagulant flow path. Alternatively, it is preferred that flow rates of up to about 12 ml/min be allowed without the pressure exceeding about 7 psig.
Further, although it is desirable to limit the free flow of anticoagulant to prevent excessive anticoagulant from being returned to the donor/patient, it is also desirable to allow at least some small residual flow rate of anticoagulant to prevent clotting. Although such a flow rate may vary with the whole blood flow rate, it is preferred to have a minimum flow rate of between about 3 to 7 ml/min, and preferably about 4-6, with about 5 ml/min being generally most preferred.
Other aspects and details of the present invention are set forth in the attached drawings and the following detailed description of the drawings.